DESCRIPTION: Neurogenetic studies in Drosophila have contributed significantly to our understanding of behavioral plasticity and the underlying molecular mechanisms. This project is a continuation of our long-term efforts to bridge the gap between these two levels of approach by elucidating the associated modifications in neuronal function and structure and in neural circuit performance. A combination of genetic, molecular, morphological and physiological techniques will be employed to analyze a collection of mutants selected for distinct behavioral alterations with identified molecular defects. Previous studies from this lab have demonstrated altered neuronal firing patterns and synaptic plasticity, as well as the abnormal habituation process of an escape circuit, in the memory mutants dnc and rut with defective cAMP metabolism and in the K+channel mutants Hk and eag. This grant proposes to continue to investigate the roles of second messenger cascades at the neuronal and circuit levels, extending from the cAMP cascade (dnc and rut) to mutations that affect CaM kinase (ala), and cGMP-dependent kinase (for). Like dnc and rut, ala mutants show learning disabilities, while for exhibits altered foraging behavior. Double mutants have been constructed for analyzing effects derived from convergence and cross talk between different signal transduction pathways. In addition, K+ channels control neuronal firing properties and are known as the targets of modulation by second messenger cascades. Mutations of different K+channel subunits, Sh and slo, as well as Hk and eag, will be examined in parallel to determine how they affect synaptic plasticity and circuit performance. This study will include the habituation, a non-associative conditioning process, in the adult escape circuit, and the plasticity of synaptic efficacy and terminal sprouting in the larval neuromuscular junctions. Analysis of firing properties and synaptic function in central neurons will be facilitated by the giant neuron culture system.